Clinical Trials /

A Study Evaluating MM-310 in Patients With Solid Tumors

NCT03076372

Description:

MM-310 is a liposomal formulation of a docetaxel prodrug that targets the EphA2 receptor on cancer cells. Docetaxel is an approved chemotherapeutic drug.This study is a Phase 1 open-label study of MM-310 in patients with solid tumors. In the first part of the study, MM-310 will be assessed as a monotherapy until a maximum tolerated dose (MTD) is established. After an MTD of MM-310 as a monotherapy is established, an expansion cohort and MM-310 in combination with other therapies will be assessed.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Endometrial Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Prostate Adenocarcinoma
  • Small Cell Lung Carcinoma
  • Soft Tissue Sarcoma
  • Urothelial Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating MM-310 in Patients With Solid Tumors
  • Official Title: A Phase-1 Study Evaluating the Safety, Pharmacology and Preliminary Activity of MM-310 in Patients With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: MM-310-01-01-01
  • NCT ID: NCT03076372

Conditions

  • Solid Tumors
  • Urothelial Carcinoma
  • Gastric Carcinoma
  • Squamous Cell Carcinoma of the Head and Neck
  • Ovarian Cancer
  • Pancreatic Ductal Adenocarcinoma
  • Prostate Adenocarcinoma
  • Non-small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Triple Negative Breast Cancer
  • Endometrial Carcinoma
  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
MM-310MM-310 monotherapy

Purpose

MM-310 is a liposomal formulation of a docetaxel prodrug that targets the EphA2 receptor on cancer cells. Docetaxel is an approved chemotherapeutic drug.This study is a Phase 1 open-label study of MM-310 in patients with solid tumors. In the first part of the study, MM-310 will be assessed as a monotherapy until a maximum tolerated dose (MTD) is established. After an MTD of MM-310 as a monotherapy is established, an expansion cohort and MM-310 in combination with other therapies will be assessed.

Trial Arms

NameTypeDescriptionInterventions
MM-310 monotherapyExperimentalMM-310 will be administered by IV infusion over 90 minutes on the first day of each 21 day cycle.
  • MM-310

Eligibility Criteria

        Inclusion Criteria:

          -  Must have one of the following cancers, for which the patient has either received or
             been intolerant to all therapy known to confer clinical benefit

               -  Urothelial carcinoma

               -  Gastric/gastroesophageal junction/esophageal carcinoma (G/GEJ/E)

               -  Squamous Cell Carcinoma of the Head and neck (SCCHN)

               -  Ovarian cancer

               -  Pancreatic ductal adenocarcinoma (PDAC)

               -  Prostate adenocarcinoma (PAC)

               -  Non-small cell lung cancer (NSCLC)

               -  Small cell lung cancer (SCLC)

               -  Triple negative breast cancer (TNBC)

               -  Endometrial carcinoma

               -  Soft tissue sarcoma subtypes except GIST, desmoid tumors and pleomorphic
                  rhabdomyosarcoma

          -  Able to provide informed consent, or have a legal representative able and willing to
             do so

          -  ≥ 18 years of age

          -  Availability of a cancerous lesion amenable to biopsy and willing to undergo a
             pre-treatment biopsy

          -  ECOG Performance Status of 0 or 1

          -  Adequate bone marrow reserve as evidenced by:

               -  ANC > 1,500/µl (unsupported by growth factors) and

               -  Platelet count > 100,000/µl

               -  Hemoglobin > 9 g/dL

          -  Patients must have adequate coagulation function as evidenced by prothrombin time
             (PT), activated partial thromboplastin time (aPTT) and international normalized ratio
             (INR) within normal institutional limits

          -  Adequate hepatic function as evidenced by:

               -  Serum total bilirubin ≤ ULN

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.

               -  Alkaline phosphatase ≤ 2.5 x ULN, unless the elevated alkaline phosphatase is due
                  to bone metastasis.

               -  In case alkaline phosphatase is >2.5 x ULN patients are eligible for inclusion if
                  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 x ULN

          -  Adequate renal function as evidenced by a serum/plasma creatinine < 1.5 x ULN

          -  Recovered from the effects of any prior surgery, radiotherapy or other antineoplastic
             therapy to CTCAE v4.03 grade 1, baseline or less, except for alopecia

          -  Women of childbearing potential or fertile men and their partners must be willing to
             abstain from sexual intercourse or to use an effective form of contraception during
             the study and for 6 months following the last dose of MM-310.

        Exclusion Criteria:

          -  Prior treatment with docetaxel within 6 months of study enrollment

          -  Pregnant or lactating

          -  Treatment with systemic anticoagulation (e.g. warfarin, heparin, low molecular weight
             heparin, anti-Xa inhibitors, etc.) except aspirin

          -  Any evidence of hematemesis, melena, hematochezia, ≥ grade 2 hemoptysis, or gross
             hematuria

          -  Any history of hereditary bleeding disorders

          -  Presence of an active infection or with an unexplained fever > 38.5°C during screening
             visits or on the first scheduled day of dosing, which in the investigator's opinion
             might compromise the patient's participation in the trial or affect the study outcome.
             At the discretion of the investigator, patients with tumor fever may be enrolled

          -  Known CNS metastases

          -  Known hypersensitivity to the components of MM-310, or docetaxel

          -  Prior treatment with MM-310

          -  Received treatment, within 28 days or 5 half-lives, whichever is shorter, prior to the
             first scheduled day of dosing, with any investigational agents that have not received
             regulatory approval for any indication or disease state and all prior clinically
             significant treatment related toxicities have resolved to Grade 1 or baseline

          -  Received other recent antitumor therapy including any standard chemotherapy or
             radiation within 14 days (or have not yet recovered from any actual toxicities of the
             most recent therapy) prior to the first scheduled dose of MM-310

          -  Received any anti-cancer drug known to have anti-VEGF/VEGFR activity within a period
             of 5 half-lives of this drug (e.g. 100 days for bevacizumab, 75 days for ramucirumab)
             prior to the first scheduled dose of MM-310

          -  Clinically significant cardiac disease, including: NYHA Class III or IV congestive
             heart failure, unstable angina, acute myocardial infarction within six months of
             planned first dose, arrhythmia requiring therapy (including torsades de pointes, with
             the exception of extrasystoles, minor conduction abnormalities, or controlled and well
             treated chronic atrial fibrillation)

          -  Patients who are not appropriate candidates for participation in this clinical study
             for any other reason as deemed by the investigator

          -  Patients who received organ or allogeneic bone marrow or peripheral blood stem cell
             transplants

          -  Chronic use of corticosteroids more than 10mg daily prednisone equivalent during the
             past 4 weeks prior to planned start of MM-310

          -  Concomitant use of strong inhibitors of CYP3A

          -  Patients with peripheral neuropathy of grade 2 or higher
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of MM-310 monotherapy administered once every 3 weeks in patients with metastatic solid tumors.
Time Frame:18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Serum levels of analytes that comprise MM-310
Time Frame:18 months
Safety Issue:
Description:
Measure:Adverse event profile using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Time Frame:18 months
Safety Issue:
Description:
Measure:Presence of human anti-human antibodies to MM-310
Time Frame:18 months
Safety Issue:
Description:
Measure:Objective responses based on RECIST v1.1 or other relevant criteria
Time Frame:18 months
Safety Issue:
Description:
Measure:Disease Control Rate
Time Frame:18 months
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merrimack Pharmaceuticals

Trial Keywords

  • Cancer
  • Oncology
  • Phase I
  • Gemcitabine
  • Carboplatin
  • MM-310
  • EphA2
  • Ephrin A2
  • Solid tumors
  • urothelial carcinoma
  • gastric carcinoma
  • squamous cell carcinoma of the head and neck
  • ovarian cancer
  • pancreatic ductal adenocarcinoma
  • prostate adenocarcinoma
  • non-small cell lung cancer
  • small cell lung cancer
  • triple negative breast cancer
  • endometrial carcinoma
  • soft tissue sarcoma
  • Merrimack

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